Functionalizing Sgc8-Paclitaxel Conjugates with F-Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety.

Recent advancements in cancer treatment have improved patient prognoses, but chemotherapy-induced cardiotoxicity remains a prevalent concern. This study explores the potential of F-base-modified aptamers for targeted drug delivery, focusing on their impact on cardiotoxicity. From the phosphoramidite, F-base functionalized Sgc8-F23 was prepared in an automated and programmable way, which was further reacted with Paclitaxel (PTX) to give the F-base modified aptamer Sgc8-paclitaxel conjugates (Sgc8-F23-PTX) efficiently. The conjugate exhibits prolonged circulation time and enhanced efficacy as precision anticancer drug delivery system. Echocardiographic assessments reveal no exacerbation of cardiac dysfunction post-Acute Myocardial Infarction (AMI), and no pathological changes or increased apoptosis in non-infarcted cardiac regions. Autophagy pathway analysis shows no discernible differences in Sgc8-F23-PTX-treated cardiomyocytes compared to controls, contrasting with increased autophagy with Nanoparticle albumin-bound -Paclitaxel (Nab-PTX). Similarly, apoptosis analysis shows no significant distinctions. Moreover, Sgc8-F23-PTX exhibits no inhibitory effects on hERG, hNav1.5, or hCav1.2 channels. These findings suggest the safety and efficacy of F-base-modified Sgc8 aptamers for targeted drug delivery, holding potential clinical applications. Further research is warranted for clinical translation and exploration of other drug carriers.

BMP6 knockdown enhances cardiac fibrosis in a mouse myocardial infarction model by upregulating AP-1/CEMIP expression.

BACKGROUND: The cardiac repair process following a myocardial infarction is a key factor in patient prognosis. In this repair process, cardiac fibrosis takes a critically important role. Among those featured genes for fibrosis, transforming growth factor beta (TGF-ß) is known to be involved in the fibrosis in various organs. And bone morphogenetic protein (BMP)6 belongs to the TGF-ß superfamily. Although BMPs are known to play exclusive roles in cardiac repair processes, the character of BMP6 in cardiac remodelling remains unclear. PURPOSE: This study aimed to investigate how BMP6 functioned in cardiac fibrosis following myocardial infarction (MI). RESULTS: In this paper, we demonstrated that BMP6 expression was upregulated after myocardial infarction in wild-type (WT) mice. Furthermore, BMP6-/- mice showed a more significant decline in cardiac function and lower survival curves after MI. An enlarged infarct area, increased fibrosis and more pronounced inflammatory infiltration were observed in BMP6-/- mice compared to WT mice. The expression of collagen I, collagen III and α-SMA was increased in BMP6-/- mice. In vitro, through gain-of-function and loss-of-function experiments, it was demonstrated that BMP6 decreases collagen secretion in fibroblasts. Mechanistically, knocking down BMP6 promoted AP-1 phosphorylation, which in turn promotes CEMIP expression, led to an acceleration in the progression of cardiac fibrosis. Finally, it was found that rhBMP6 would alleviate ventricular remodelling abnormalities after myocardial infarction. CONCLUSION: Therefore, BMP6 may be a novel molecular target for improving myocardial fibrosis and cardiac function after myocardial infarction.

Metal-free visible-light-driven cascade cyclization reaction to synthesize 2-oxindoles via benzoyl and phenylsulfinyl radicals with acrylamide derivatives.

A metal-free visible-light-driven cascade cyclization reaction to synthesize 3-methyl-3-acetophenone-2-oxindoles and 3-methyl-3-(methylsulfonyl)benzene-2-oxindoles in yields up to 96% and 99%, via benzoyl and phenylsulfinyl radicals with acrylamide derivatives is reported, respectively. Extensive studies, including gram-scale, radical capture and isotope experiments, were performed to indicate that the reaction may involve a radical process.

[Direct determination of copper, iron and sodium in high-purity alumina by slurry introduction furnace atomic absorption spectrometry with Smith-Hieftje background correction].

Direct determination of copper, iron and sodium in high-purity alumina was performed by slurry-furnace atomic absorption spectrometry with Smith-Hieftje background correction (S-H-GFAAS). Instrument conditions of GFAAS such as pyrolysis, atomization and hollow cathode lamp current by S-H background correction were optimized, and the optimal experimental conditions were selected. Calibration was performed using aqueous standards method for sample analysis. The accuracy of the proposed method was shown for the case of Al2O3 (AKP-30), and compared with those obtained by furnace atomic absorption spectrometry subsequent to decomposition by sulfuric acid in PTFE pressure vessels. The results were in agreement well with values found in the literature by different methods. It is a simple, convenient and accurate method and it is suitable for the rapid analysis of trace element in alumina. The linear regression coefficients of the calibration curves were better than 0.999 0. The detection limits were 0.66, 2.5 and 0.13 ng x g(-1), respectively, with a relative standard deviation being not more than 5.2%.

[Research advance in slurry introduction for graphite furnace atomic absorption spectrometry].

Slurry introduction graphite furnace atomic absorption spectrometry combining the significant advantages of the solid and liquid sampling methods is already considered as a mature technique. It was widely utilized for metal determination in trace and even ultra trace analysis in organic and inorganic complicated matrix, even for routine analysis. Methodology of the analysis of various materials using slurry furnace atomic absorption spectrometry was reviewed in the present paper in late 10 years. Techniques of slurry preparation (liquid media, stabilizing agents, mass/volume ratio, particle size and slurry homogenization systems), the chemical modification, background correctors, calibration, precision and trueness of analysis were described in detail. The developing trend has also presented. Eighty one references were cited.

[Influence of meliorated AS-PCR primer for ABO genotyping].

OBJECTIVE: To improve the correct rate of ABO genotyping by meliorating AS-PCR primer. METHODS: The primer P1 was changed into primer P1' by substituting the fifth base G for C of 3' end and the ABO genotyping results of primer P1 and P1' was compared and analysed. RESULTS: The non-specific product of OO typing is reducing and the wrong genotyping of OO and AO was avoided by meliorating AS-PCR primer. CONCLUSION: The rates of wrong ABO genotyping results could be effectively reduced by using altering primer P1'.

[Identification of six species of sarcosaphagous flies (Diptera) by sequence analysis of cytochrome oxidase subunit I gene (COI) in Weifang].

OBJECTIVE: To identify sarcosaphagous flies and their larvae, pupa. METHODS: Sarcosaphagous flies and their larvae, pupas were collected from human corpses and their surroundings in the Weifang city. A 304 bp region in COI gene was analyzed by mtDNA sequencing. RESULTS: The studied region showed no sequence divergence within same species and significant difference were found between different species in all samples. CONCLUSION: It is a practical approach to identify these Sarcosaphagous flies and their larvae, pupas by sequence analysis of the 304bp region of the COI in mtDNA.

Han nation population in Shangdong province of china data for nine STR loci.

Allele frequencies for nine STR loci (D3S1358, TH01, TPOX, CSF1PO, D16S539, D7S820, D2S1338, D8S1179, D18S535) were obtained from a sample of 100/86 unrelated healthy individual born in Shangdong province of China. chi(2)-Test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium.

Quantitative determination of geosmin in red beets (Beta vulgaris L.) using headspace solid-phase microextraction.

An improved analytical method for the determination of geosmin in red beets was developed using headspace solid-phase microextraction (HSPME). Volatiles of beet juice were extracted in headspace for 2 h using a polydimethylsiloxane/divinylbenzene fiber, thermally desorbed from the fiber, and analyzed by gas chromatography. The HSPME method was determined to be suitable for geosmin analysis as evidenced by high relative recovery (99.2%), low relative standard deviation (7.48%), and reasonable detection limit (1 microg/kg of beet root tissue). The concentrations of geosmin in four beet cultivars ranged from 9.69 +/- 0.22 to 26.7 +/- 0.27 microg/kg, depending on cultivar.

Biosynthetic origin of geosmin in red beets (Beta vulgaris L.).

Geosmin provides the characteristic but sometimes undesirable "earthy" flavor to red table beets. To date, it is not known whether geosmin is a byproduct of beet metabolism or synthesized by soil-borne microorganisms and taken up by the beets during maturation. Analysis of mature beet roots revealed that peels contained 6 times the amount of geosmin compared to the bodies and cores. Sterilized beet seeds were aseptically grown in a basal medium prior to analysis for the presence of geosmin. Using a headspace solid-phase microextraction (HSPME) method, the relative recovery of geosmin from beet seedling extracts was 72.0 +/- 4.2% with (-)-menthone as the internal standard. The presence of geosmin in aseptically grown beet seedlings was confirmed by gas chromatography-mass spectrometry using authentic geosmin as the standard. During aseptic growth, the concentration of geosmin in seedlings remained constant for up to 5 months but increased at 6 months. Geosmin added to the growth medium was not absorbed by the seedlings. These studies support the conclusion that red beets are capable of endogenous synthesis of geosmin.

[Genetic polymorphism of 9 STR loci in Han nation population in Shandong Province].

OBJECTIVE: To study genetic polymorphism of 9 STR loci in Han nation population in Shangdong Province. METHODS: We investigated 100 unrelated individuals of Han nation population in Shandong Province and studied their genetic distribution of 9 STR loci and Amelogenin locus. Primers of 10 loci were labeled with the NHS-ester fluorescent dye 5-FAM (blue), Joe (green) or NED (yellow). The data of Han nation population were generated by multiple amplification and subjected to GeneScan, genotype and genetic distribution analysis. RESULTS: 83 alleles and 220 genotypes were observed, with the corresponding frequency of 0.0050-0.4050 and 0.0100-0.2100. The average of heterozygosity was 0.7778, the accumulated discrimination power was 0.9999. The accumulated probability of exclusion paternity was 0.9999. The polymorphism information content was 0.5823-0.8396. CONCLUSIONS: Chi-Square test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium.